DeCure for Intellectual developmental disorder with short stature and behavioral abnormalities
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for intellectual developmental disorder with short stature and behavioral abnormalities — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntellectual developmental disorder with short stature and behavioral abnormalities maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for intellectual developmental disorder with short stature and behavioral abnormalities is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
IQ motif and Sec7 domain ArfGEF 1 (IQSEC1) — IQSEC1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 2~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6FNE · 2.501 Å · ligand (2~{S})-6-methyl-5-nitro-2-(trifluoromethyl)-2,3-dihydrochromen-4-one (DY5). Experimental structure, not a prediction.
What the evidence adds up to
De novo heterozygous variants in RNU4-2, a component of the major spliceosome, were recently found to cause a neurodevelopmental disorder that may be one of the most common monogenic causes of neurodevelopmental conditions. Four novel affected individuals were reported in 2024, two identified by targeted sequencing based solely on facial features resembling the first patient, suggesting a recognisable morphological phenotype. The condition is characterised by developmental delay, intellectual disability, microcephaly, short stature and hypotonia. The authors note this facial gestalt could aid diagnosis in resource-limited regions where whole genome sequencing is unavailable, and for retro-active prioritisation of individuals with negative genetic testing.
A 2021 report describes a boy aged 4 years 6 months with height 76.5 cm (–6.3 SD), IQ of 30, cerebellar volume loss, and no external anomaly or microcephaly. Family history suggested X-linked recessive inheritance: his mother had mild intellectual disability with normal stature, his maternal uncle had severe mental retardation with remarkably short stature. Whole-exome sequencing identified a novel frameshift mutation in the KDM5C gene (NM_004187: exon 23: c.3874_3875del: p.Ala1292Glnfs*7). The mother was a heterozygous carrier. The authors suggest KDM5C disorder should be considered when patients present with remarkably short stature and X-linked mental retardation.
A 1984 controlled study of 24 children with constitutional short stature compared to 23 matched controls found no differences on tests of intellectual, academic or visual-motor functioning. The authors state that while children with constitutional delay have been shown to exhibit low self-esteem and high levels of internalizing behaviour problems, these difficulties do not appear to intrude significantly into the intellectual or academic realms. This contradicts uncontrolled studies that had suggested learning problems.
What is still missing is prospective data on the full phenotypic range of RNU4-2-related disorder, particularly in larger cohorts with standardised cognitive and growth assessments. For KDM5C, only single-case reports exist, and no systematic screening of short-stature populations for this gene has been done. The 1984 study is decades old and used a different definition of constitutional delay; no modern replication with genetic confirmation exists. No trial has tested any intervention for intellectual disability or short stature in any of these genetic groups. Money for large-scale sequencing of short-stature cohorts, trial design for targeted therapies, and patient stratification by molecular diagnosis are all lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 2024 · 14 citations
<scp>RNU4‐2</scp> ‐Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt
AbstractDe novo heterozygous variants in RNU4-2, a component of the major spliceosome, were recently found to cause a novel neurodevelopmental disorder. Preliminary evidence suggests that this newly discovered syndrome is one of the most common monogenic causes of neurodevelopmental disorders. It is characterised by developmental delay and intellectual disability, microcephaly, short stature and hypotonia. However, much remains to be elucidated regarding the phenotype of the affected individuals. We report on four novel individuals affected by the condition, two of which were identified following targeted sequencing based solely on the facial features that were similar to those of the first patient we identified. This strongly suggests that this syndrome entails a recognisable morphological phenotype, which is particularly relevant for resource-limited regions where whole genome sequencing is not readily available, and in view of retro-active selection/prioritisation of individuals with hitherto negative genetic testing.
Journal of Learning Disabilities · 1984 · 11 citations
Do Children with Constitutional Delay Really Have More Learning Problems?
AbstractTo assess the effects of constitutional short stature on intellectual, academic and visual-motor functioning, we administered a battery of psychological tests to a group of 24 such children. Their responses were compared to those of 23 subjects with normal height matched for age, sex and socioeconomic status. Contrary to the conclusions of uncontrolled studies, our data showed short and control groups to be comparable on all variables. While children with constitutional delay have been shown to exhibit low self-esteem and high levels of internalizing behavior problems, these difficulties do not appear to intrude significantly into the intellectual or academic realms.
X-linked mental retardation and severe short stature with a novel mutation of the <i>KDM5C</i> gene
AbstractMany monogenetic disorders of short stature have autosomal recessive/dominant form of inheritance. However, X-linked short stature has not been well recognized. Herein, we report a case of a boy from a family with familial severe short stature and mental retardation, who displayed an X-linked recessive trait. The boy at the age of 4 yr and 6 mo presented with remarkable growth failure (height: 76.5 cm [–6.3 SD]) and mental retardation (IQ: 30) and cerebellar volume loss and without an external anomaly or microcephaly to our hospital. A careful interview to determine the family history suggested a genetic background of familial mental retardation and short stature. His mother had mild intellectual disability with normal stature and his maternal uncle had severe mental retardation with remarkably short stature. Whole-exome sequencing identified a pathogenic variant in the KDM5C gene, NM_004187: exon 23: c.3874_3875del: (p.Ala1292Glnfs*7). He presented with a novel frameshift mutation. His mother was a heterozygous carrier of the variant. This case suggests that a disorder associated with the KDM5C gene should be considered when patients present with remarkably short stature and X-linked mental retardation.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
